Elderly individuals with mild cognitive impairment (MCI) are at high risk for developing dementia, including Alzheimer's disease. Previous studies have proposed that elevated plasma homocysteine might be a risk factor for dementia. However, the impact of plasma homocysteine on MCI remains controversial. We investigated the relation between hyperhomocysteinemia and the risk of MCI in an elderly Korean population. A total of 1215 elderly subjects (aged 60-85 y) were selected from the Ansan Geriatric study to participate in this study. MCI was diagnosed on the basis of the Mayo Clinic criteria. Mean plasma homocysteine concentrations were higher in elderly subjects with MCI than in normal elderly subjects (17.6 +/- 7.4 vs. 15.7 +/- 4.8 micromol/L; P < 0.001). Subjects with hyperhomocysteinemia (>15 micromol/L) also had a higher prevalence of MCI. The unadjusted OR for MCI was greater in subjects with hyperhomocysteinemia than in normal subjects and it increased according to the degree of hyperhomocysteinemia (OR = 1.39; 95% CI = 1.09-1.79 vs. OR = 2.61; 95% CI = 1.22-5.61). These trends did not differ after adjustment for age, sex, and other putative risk factors for cognitive dysfunction (OR = 1.40; 95% CI = 1.07-1.83 vs. OR = 2.40; 95% CI = 1.08-5.31). In conclusion, hyperhomocysteinemia may be an independent risk factor for MCI in elderly Koreans. A causal relationship between plasma homocysteine levels and cognitive impairment should be evaluated in a follow-up study of elderly Korean subjects.